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Overexpression of estrogen receptor beta alleviates the toxic effects of beta-amyloid protein on PC12 cells via non-hormonal ligands

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Neural Regeneration Research 2012年第14期7卷 1095-1100页

作者： Hui Wang Lihui Si Xiaoxi Li Weiguo Deng Haimiao Yang Yuyan Yang Yan Fu Department of Gynaecology and Obstetrics First Hospital of Jilin University Changchun 130021 Jilin Province China Department of Gynaecology and Obstetrics Second Hospital of Jilin University Changchun 130044 Jilin Province China Department of Gynaecology Affiliated Hospital of Changchun University of Traditional Chinese Medicine Changchun 130021 Jilin Province China Department of Children＇s Heatlh School of Public Health Jilin Univeristy Changchun 130021 China Department of Scientific Research Affiliated Hospital of Changchun University of Traditional Chinese Medicine Changchun 130021 China Department of Gynaecology and Obstetrics Minzu Hospital of Yitong County Yitong 130700 Jilin Province China

After binding to the estrogen receptor, estrogen can alleviate the toxic effects of beta-amyloid protein, and thereby exert a therapeutic effect on Alzheimer＇s disease patients. estrogen can increase the incidence of breast carcinoma and endometrial cancer in post-menopausal women, so it is not suitable for clinical treatment of Alzheimer＇s disease. There is recent evidence that the estrogen receptor can exert its neuroprotective effects without estrogen dependence. Real-time quantitative PCR and flow cytometry results showed that, compared with non-transfected PC12 cells, adenovirus-mediated estrogen receptor β gene-transfected PC12 cells exhibited lower expression of tumor necrosis factor a and interleukin 1β under stimulation with beta-amyloid protein and stronger protection from apoptosis. The Akt-specific inhibitor Abi-2 decreased the anti-inflammatory and anti-apoptotic effects of estrogen receptor β gene-transfection. These findings suggest that overexpression of estrogen receptor β can alleviate the toxic effect of beta-amyloid protein on PC12 cells, without estrogen dependence. The Akt pathway is one of the potential means for the anti-inflammatory and anti-apoptotic effects of the estrogen receptor.

关键词： estrogen estrogen receptor β Alzheimer＇s disease beta-amyloid protein adenovirus neural regeneration

Expressions of estrogen receptor subtypes and c-met proto-oncogene in endometrial carcinoma and their correlation

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Journal of Pharmaceutical Analysis 2010年第1期22卷 54-58页

作者： Yue-Ling Wang,Wei-Dong Dai,Jiang-Fen Wang,Lin Liu Department of Obstetrics and Gynecology,the First Affiliated Hospital,Medical School of Xi’an Jiaotong University,Xi’an 710061,China Department of Obstetrics and Gynecology First Affiliated Hospital Medical School of Xi'an Jiaotong University Xi'an 710061 China

Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.

关键词： estrogen receptor α estrogen receptor β c-met proto-oncogene endometrial carcinoma

Association of a cytosine-adenine repeat polymorphism in the estrogen receptor β gene with occurrence and severity of rheumatoid arthritis

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Open Journal of Internal Medicine 2013年第1期3卷 3-7页

作者： Kanako Watanabe Hiromi Sato Ayano Ito Tomomi Sato Aránzazu González-Canga Hana Sugai Masahiko Suzuki Takao Namiki Koichi Ueno Department of Geriatric Pharmacology and Therapeutics Graduate School of Pharmaceutical SciencesChiba UniversityChibaJapan Assessment Area Medicines for Veterinary Use DepartmentAgencia Espanola de Medicamentosy Productos Sanitarios(AEMPS)MadridSpain Research Center for Frontier Medical Engineering Chiba UniversityChibaJapan Department of Frontier Japanese-Oriental(Kampo)Medicine Graduate School of MedicineChiba UniversityChibaJapan

We investigated the influence of the cytosine-adenine (CA) dinucleotide repeat polymorphism in intron 6 of estrogen receptor β (ERβ) gene on rheumatoid arthritis (RA) risk. One hundred and ninety-three RA patients and 77 control subjects with osteoarthritis (OA) were recruited. The CA repeat polymorphism was assayed by a dye-terminator cycle sequencing analysis. No statistically significant difference in the mean number of CA repeats between the RA and OA patients was observed (RA: 21.47, OA: 21.23, P = 0.324). The alleles were categorized according to the number of repeats: short (S, ≦21) and long (L, ≧22), in which the genotypes SS, SL, and LL were observed. No significant differences were observed for the allele and genotype distributions of this polymorphism in both patient groups. The RA patients were classified according to RA severity: mild (least erosive disease) and severe (more erosive and mutilating disease). Again, no significant difference in genotype frequency between these groups was observed, even after stratifying by sex. The present study indicates that additional studies are needed to clarify the roles of this polymorphism, estrogen, and ER in the development of autoimmune diseases.

关键词： Polymorphism Rheumatoid Arthritis Sex estrogen receptor β CA Repeat

Inhibitory effect of estrogen receptor beta on P2X7 receptors in inflammatory bowel disease（IBD） in rats

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Inhibitory effect of estrogen receptor beta on P2X7 receptor...

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

中国生理学会消化与营养专业委员会成立大会暨第一届学术会...

作者： Wen-xin Li Qian Jiang 马蓓 Department of Physiology Second Military Medical University Experimental training center for Basic Medical Sciences 中国人民解放军第二军医大学中国人民解放军第二军医大学基础医学实验教学中心

Objective estrogen receptor beta（ERβ）and P2X7 receptors（P2X7R）have been shown to play therapeutic roles in inflammatory bowel disease（IBD）.However the mechanisms underlying how ERβexerts therapeutic effects and its relationship with P2X7R in rats with inflammation are not known.The present study is to investigate the role and the underlying mechanisms of ERβactivation in the treatment of chronic inflammation including IBD and its relationship with P2X7R.Methods:In our study animal behavior tests immunofluorescence technique western blotting ELISA and lentiviral transfection were used to determine the therapeutic effect of ERβin rats and the underlying mechanisms of its relation with P2X7R.Results:（1）ERβ receptors and P2X7 receptors were co-expressed in both RAW264.7 macrophages and the isolated macrophages of colorectum in rats.（2）Activation of P2X7 receptors significantly promoted the initiation and development of the colonic inflammation including the more weight loss increased DAI scores and the release of IL-1β.（3）ERβ but not ERαagonists significantly inhibited the initiation and development of colonic inflammation.（4）Activation of ERβ significantly inhibited the expression and function of P2X7 receptors in colorectum in IBD rats.（5）The JAK2-STAT3 signaling pathway was involved in both the therapeutic role of ERβ activation in the colonic inflammation and the inhibitory role of P2X7R expression and function.Conclusion:These results suggest that ERβ activation plays an important therapeutic role in colonic inflammation through down-regulation of P2X7R in colorectum probably via JAk2-STAT3 signaling pathway which might provide a novel therapeutic strategy for clinical treatment of IBD.

关键词： estrogen receptor β P2X7 receptors Inflammatory bowel disease Microphage IL-1β

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Inhibitory effect of estrogen receptor beta on P2X3 receptor...

Occurrence of lymphoma in non-gonadal organ during pregnancy: a report on four cases and literature review

中国生理学会消化与营养专业委员会成立大会暨第一届学术会...

作者： Wen-xin Li Qian Jiang Juan Fan 马蓓 Department of Physiology Second Military Medical University Experimental training center for Basic Medical Sciences 中国人民解放军第二军医大学中国人民解放军第二军医大学基础医学实验教学中心

Objective It has been reported that estrogen receptor beta（ERβ）might play a therapeutic role in inflammatory bowel disease（IBD）,while the underlying mechanism is not known.P2X3 receptors are widely accepted to be closely related to inflammation.The present study is to investigate the role and the underlying mechanisms of ERβactivation in the treatment of chronic inflammation including IBD and its relationship with P2X3R.Methods:In our study animal behavior tests visceromotor reflex recording and western blotting were used to determine whether the therapeutic effect of ERβin rats with inflammation was related with P2X3R.Results:In complete Freund adjuvant（CFA）-induced chronic inflammation in rats paw withdrawal threshold was significantly decreased which were then reversed by systemic injection of ERβagonists DPN or ERB-041.In 246-trinitrobenzene sulfonic acid（TNBS）-induced colitis in rats weight loss higher DAI scores increased visceromotor responses and inflammatory responses were reversed by application of DPN or ERB-041.The higher expressions of P2X3R in dorsal root ganglia（DRG）of CFA-treated rats and those in colorectum and DRG of TNBS-treated rats were all decreased by injection of DPN or ERB-041.Mechanical hyperalgesia and increased P2X3 expression in ovariectomized（OVX）CFA-treated rats were reversed by estrogen replacements.Furthermore the expressions of extracellular signal-regulated kinase（ERK）in DRG and spinal cord dorsal horn（SCDH）and c-fos in SCDH were significantly decreased after estrogen replacement compared with those of OVX rats.The ERK antagonist U0126 significantly reversed mechanical hyperalgesia in the OVX rats.Conclusion:These results suggest that estrogen may play an important therapeutic role in inflammation through down-regulation of P2X3R in peripheral tissues and the nervous system probably via ERβsuggesting a novel therapeutic strategy for clinical treatment of inflammation.

关键词： estrogen receptor β P2X3 receptor CFA TNBS Inflammation

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Cancer Biology & Medicine 2016年第3期13卷 399-403页

作者： Da-Lin Gao Qian-Qian Fu Tian-Tian Zhang Lin Sun Yi Pan Qiong-Li Zhai Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin Key Laboratory of Cancer Prevention and Therapy

Lymphoma rarely occurs during pregnancy, making this condition difficult to define. Lymphomas that occur in reproductive organs during pregnancy exhibit unique clinical characteristics. Among the limited cases, non-Hodgkin's lymphoma(NHL) shows a considerably higher incidence rate than Hodgkin's lymphoma(HL); NHL also displays clinical characteristics, such as high aggressiveness, advanced stage, and poor outcome. This study reports on four cases of lymphomas in non-gonadal organs(HL,n=2; NHL, n=2) during pregnancy. The tumors rapidly progressed in all patients during pregnancy but remitted at the end of pregnancy and/or therapy. The two HL cases were nodular sclerosis classical HL and treated with chemotherapy after terminating the pregnancy. One of the NHL cases was primary cutaneous follicular center lymphoma, a B cell-derived indolent lymphoma.The patient was followed up without any therapy after terminating her pregnancy. The other case was a follicular lymphoma grade3 B, which was treated with chemotherapy after delivery. We also conducted a literature review of 165 lymphoma cases occurring during pregnancy reported from 1976 to 2013 to reveal the correlation between pregnancy and lymphoma progression.Immunohistochemistry studies were performed to determine the expression of estrogen/progesterone receptors(ER/PR), and ER was weakly positive and sporadic. We concluded that lymphomas occurring during pregnancy should be managed with a prompt and reasonable treatment. High estrogen level in maternal body may affect lymphoma progression.

关键词： Lymphoma pregnancy estrogen estrogen receptor β BCL2

Epigenetic Regulation of the ERβ Gene on the estrogen Signal Transfection Pathway in Colon Cancer Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2010年第1期30卷 69-74页

作者：翟荣林王国斌蔡开琳陶凯雄许飞张万里王智勇 Department of General Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

We studied the regulatory effects of the estragen receptorβ(ERβ)gene on the downstream estrogen signal transfection pathway in colon cancer cells and the possible mechanisms involved.A human ERβ gene recombinant expression plasmid,pEGFP-C1-ERβ,was constructed and transfected into the Caco-2 colon cancer cell line,a line with low ERβ gene expression.The expression of ERβ mRNA and protein was detected 72h after transfection.RT-PCR was used to examine the expression levels of the progesterone recepror(PR)gene ...

关键词： estrogen receptor β signal transfection methylation colon cancer epigenetics